Protein-Protein Interactions Shape Genomic Autoimmunity in the Adaptively Evolving Rhino-Deadlock-Cutoff Complex.
Protein-Protein Interactions Shape Genomic Autoimmunity in the Adaptively Evolving Rhino-Deadlock-Cutoff Complex.
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DOI：
10.1093/gbe/evab132
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发表时间：
2021-07-06
影响因子：
3.3
通讯作者：
Kelleher ES
中科院分区：
文献类型：
--
作者：
Kelleher ES
piwi相互作用RNA （piRNA）途径是一种基因组防御系统，通过转录和转录后沉默控制转座因子（te）的运动。尽管TE防御对于确保种系基因组完整性至关重要，但同样重要的是，piRNA途径以沉默宿主基因的形式避免自身免疫。为了扩大对入侵te的控制而进行的选择循环，以及为了减少对宿主基因的影响而增加特异性的选择，被提出来解释piRNA途径蛋白中适应性进化的频繁特征。然而，对该模型的实证检验仍然有限，特别是在针对基因组自身免疫的选择方面。我检查了三种适应性进化的piRNA蛋白，Rhino， Deadlock和Cutoff，以证明黑腹果蝇和拟果蝇之间自身免疫的种间差异。我测试了自身免疫假说的一个关键预测，即由于缺乏针对脱靶效应的历史选择，外源异源piRNA蛋白将表现出增强的自身免疫。与这一预测相一致的是，全长D. simulans Cutoff以及犀牛的D. simulans hinge和chromo结构域对D. melanogaster基因的调控范围扩大。我进一步证明，这种自身免疫依赖于已知的D. simulans蛋白或结构域与其相互作用伙伴之间的不相容性。我的观察表明，在Rhino和Cutoff中，作为适应性进化界面的蛋白质-蛋白质相互作用域也决定了它们自身免疫的潜力。
The Piwi-interacting RNA (piRNA) pathway is a genomic defense system that controls the movement of transposable elements (TEs) through transcriptional and post-transcriptional silencing. Although TE defense is critical to ensuring germline genome integrity, it is equally critical that the piRNA pathway avoids autoimmunity in the form of silencing host genes. Ongoing cycles of selection for expanded control of invading TEs, followed by selection for increased specificity to reduce impacts on host genes, are proposed to explain the frequent signatures of adaptive evolution among piRNA pathway proteins. However, empirical tests of this model remain limited, particularly with regards to selection against genomic autoimmunity. I examined three adaptively evolving piRNA proteins, Rhino, Deadlock, and Cutoff, for evidence of interspecific divergence in autoimmunity between Drosophila melanogaster and Drosophila simulans. I tested a key prediction of the autoimmunity hypothesis that foreign heterospecific piRNA proteins will exhibit enhanced autoimmunity, due to the absence of historical selection against off-target effects. Consistent with this prediction, full-length D. simulans Cutoff, as well as the D. simulans hinge and chromo domains of Rhino, exhibit expanded regulation of D. melanogaster genes. I further demonstrate that this autoimmunity is dependent on known incompatibilities between D. simulans proteins or domains and their interacting partners in D. melanogaster. My observations reveal that the same protein–protein interaction domains that are interfaces of adaptive evolution in Rhino and Cutoff also determine their potential for autoimmunity.
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影响因子：
10.7
作者：
Kolaczkowski, Bryan;Hupalo, Daniel N.;Kern, Andrew D.
通讯作者：
Kern, Andrew D.
DOI：
10.1073/pnas.0605421103
发表时间：
2006-11-21
影响因子：
11.1
作者：
Naito, Ken;Cho, Eunyoung;Wessler, Susan R.
通讯作者：
Wessler, Susan R.
截止值抑制 RNA 聚合酶 II 终止，以确保 piRNA 前体的表达。
影响因子：
16
作者：
Chen YA;Stuwe E;Luo Y;Ninova M;Le Thomas A;Rozhavskaya E;Li S;Vempati S;Laver JD;Patel DJ;Smibert CA;Lipshitz HD;Toth KF;Aravin AA
通讯作者：
Aravin AA
影响因子：
3.3
作者：
Lewis SH;Salmela H;Obbard DJ
通讯作者：
Obbard DJ
影响因子：
64.5
作者：
Mohn, Fabio;Sienski, Grzegorz;Brennecke, Julius
通讯作者：
Brennecke, Julius